6-hydroxy-3-hexenyl alkoxymethyl ether compound and a process for preparing a 3,13-octadecadien-1-ol compound from the same

ABSTRACT

The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH2CH2CH=CHCH2CH2OCH2OCH2R1 (1), R1 representing a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and also relates to a process for preparing a 3,13-octadecadien-1-ol compound of the following formula (6): CH3(CH2)3CH=CH(CH2)8CH=CHCH2CH2OH (6) from the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1).

TECHNICAL FIELD

The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethylether compound and a process for preparing a 3,13-octadecadien-1-olcompound from the same.

BACKGROUND ART

Clearwing borer (Carmenta chrysophanes) is known as a pest againstpersimmon in Australia. It is reported that a proper timing fortraditional insecticide application effective for the pest is unknownand that the insecticide itself is less effective for the pest(Non-Patent Literature 1 listed below). Poplar clearwing moth(Paranthrene tabaniformis) is one of the most serious pests againstpoplar in the Northern Hemisphere, and is known to be difficult tocontrol. One of sex pheromones of Paranthrene tabaniformis is a3,13-octadecadien-1-ol compound (Non-Patent Literature 2 listed below).Accordingly, biological control methods have been attracting attention,and utilization of sex pheromone substances is expected as one of them.

The 3,13-octadecadien-1-ol compound was extracted from adult females ofCarmenta foraseminis which has recently seriously damaged cacao in SouthAmerica including Peru. This compound is thought to be a sex pheromonecandidate, and its utilization is expected (Non-Patent Literature 3listed below).

A process for preparing a 3,13-octadecadien-1-ol compound is describedin Patent Literature 1 listed below. In the process, a startingmaterial, 1-hexyne, is subjected to a coupling reaction with1,8-dibromohexane in the presence of n-butyllithium in tetrahydrofuranand hexamethylphosphoric triamide to synthesize 14-bromo-5-tetradecyne.Next, the 14-bromo-5-tetradecyne thus obtained is subjected to ahydrogenation using 5 % palladium-barium sulfate as a catalyst andquinoline as a catalyst poison so that the carbon-carbon triple bond isreduced to a carbon-carbon double bond to synthesize(5Z)-14-bromo-5-tetradecene. Subsequently, 3-butyn-1-ol and lithium arereacted with each other in the presence of ammonia and then subjected toa coupling reaction with the (5Z)-14-bromo-5-tetradecene to synthesize(13Z)-octadecen-3-yn-1-ol. Then, the carbon-carbon triple bond of the(13Z)-octadecen-3-yn-1-ol is reduced to a carbon-carbon double bond.

Another process for preparing a 3,13-octadecadien-1-ol compound isdescribed in Non-Patent Literature 5 listed below. In the process, astarting material, 1,9-nonanediol, is subjected to half bromination ofone of its hydroxyl groups with hydrogen bromide and the protection ofthe other hydroxyl group with 2,3-dihydropyran to synthesize2-[(9-bromononyl)oxy]tetrahydro-2H-pyran. Next, the2-[(9-bromononyl)oxy]tetrahydro-2H-pyran thus obtained is reacted with1-hexynyllithium in tetrahydrofuran and hexamethylphosphoric triamideand then subjected to Birch reduction with metallic lithium. Then, the2-tetrahydropyranyl group is removed to obtain 10-pentadecen-1-ol.Subsequently, the hydroxyl group of the 10-pentadecen-1-ol thus obtainedis iodinated with iodine in the presence of imidazole as a base, andtriphenylphosphine in a mixed solvent of diethyl ether and acetonitrileto synthesize 15-iodo-5-pentadecene. Next, 3-butynyl tetrahydropyranylether is reacted with n-butyllithium in tetrahydrofuran andhexamethylphosphoric triamide and then subjected to a coupling reactionwith the 15-iodo-5-pentadecene to synthesize (13E)-13-octadecen-3-yltetrahydropyranyl ether. Subsequently, (13E)-13-octadecen-3-yltetrahydropyranyl ether thus obtained is subjected to a hydrogenationusing 5 % palladium-barium sulfate as a catalyst and quinoline as acatalyst poison so that its carbon-carbon triple bond at the position 3is reduced to a carbon-carbon double bond. Finally, the2-tetrahydropyranyl group is removed.

A 3,13-octadecadienyl acetate compound is also known as a sex pheromoneof many clearwings such as Peachtree borer (Synanthedon exitiosa)(Non-Patent Literature 4 listed below). The 3,13-octadecadienyl acetatecompound is reportedly prepared by acetylating a 3,13-octadecadien-1-olcompound (Non-Patent Literature 5 listed below).

LIST OF THE LITERATURES Patent Literature

[Patent Literature 1] KR-A-180056877

Non-Patent Literatures

[Non-Patent Literature 1] Richard A Vickers et al., 2001, AustralianJournal of Entomology, 40: 69-73.

[Non-Patent Literature 2] Raimondas Mozuraitis et al., 2007, Z.Naturforsch., 62C: 138-142.

[Non-Patent Literature 3] Abstracts of the 1st Latin American Meeting ofChemical Ecology Colonia del Sacramento, Uruguay October 17-20, 2010

[Non-Patent Literature 4] D.G. Nielsen et al., 1975, Environmentalentomology, 3 (1): 451-454.

[Non-Patent Literature 5] T. Ando et al., 2006, Biosci. Biotechnol.Biochem., 70 (2): 508-516.

[Non-Patent Literature 6] Thomas J. Caggiano et al. Encyclopedia ofReagents for Organic Synthesis: 3694-3699.

PROBLEMS TO BE SOLVED BY THE INVENTION

In the preparation processes described in Patent Literature 1 andNon-Patent Literature 5, hexamethylphosphoric triamide is used as asolvent in a large amount. This solvent is carcinogenic, which makes theprocesses difficult for industrial application. Expensive palladiumcatalyst is used in the hydrogenation, which make the processeseconomically less advantageous. Quinoline used as a catalyst poison inthe processes is recently considered to adversely affect the human body,and is difficult to be used industrially. Ammonia used in the couplingreaction and Birch reduction causes a serious symptom upon inhalationeven at a low concentration and is regulated by the Offensive OdorControl Act and the High Pressure Gas Safety Act. This requires aspecial equipment and makes the processes unsuitable for industrialproduction. The processes use metallic lithium, which ignites easily incontact with water, which is unfavorable for industrial application. Theprocesses comprise many steps. Further, a double bond is formed atposition 3 by reduction in the later stage, which causes a risk that thedouble bond, at position 13, formed by reduction in the former stage isalso hydrogenated to by-produce 3-octadecen-1-ol so as to decreasepurity.

SUMMARY OF THE INVENTION

The present invention has been made in these circumstances, and aims toprovide a process for efficiently preparing 3,13-octadecadien-1-olcompounds in a high purity.

As a result of the intensive researches to overcome the aforesaidproblems of the prior art, the present inventors have found that a6-hydroxy-3-hexenyl alkoxymethyl ether compound is a useful startingmaterial for the preparation of a 3,13-octadecadien-1-ol compound. Thepresent inventors have also found that use of the 6-hydroxy-3-hexenylalkoxymethyl ether compound makes it possible to efficiently prepare the3,13-octadecadien-1-ol compound in shorter steps and in a high purity,while controlling stereoisomerisim at the position 3 and position 13,and thus have completed the present invention.

According to one aspect of the present invention, there is provided aprocess for preparing a 3,13-octadecadien-1-ol compound of the followingformula (6):

the process comprising:

halogenating a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of thefollowing general formula (1):

wherein R¹ represents a hydrogen atom, an n-alkyl group having 1 to 9carbon atoms, or a phenyl group to prepare a 6-halo-3-hexenylalkoxymethyl ether compound of the following general formula (2):

wherein X¹ represents a halogen atom, and R¹ is as defined above;

converting the 6-halo-3-hexenyl alkoxymethyl ether compound (2) into anucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound of thefollowing general formula (3):

wherein M represents Li, MgZ², CuZ², or CuLiZ², wherein Z² represents ahalogen atom or a 6-(alkoxymethoxy)-3-hexenyl group, and R¹ is asdefined above;

subjecting the nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenylcompound (3), to a coupling reaction with a 12-halo-5-dodecene of thefollowing general formula (4):

wherein X² represents a halogen atom,

to prepare a 3,13-octadecadiene alkoxymethyl ether compound of thefollowing general formula (5):

wherein R¹ is as defined above; and

dealkoxymethylating the 3,13-octadecadiene alkoxymethyl ether compound(5) to prepare the 3,13-octadecadien-1-ol compound (6).

According to another aspect of the present invention, there is provideda process for preparing a 3,13-octadecadienyl acetate compound of thefollowing formula (7):

wherein Ac represents an acetyl group, the process comprising:

-   the aforesaid process for preparing the 3,13-octadecadien-1-ol    compound (6), and-   acetylating the resulting 3,13-octadecadien-1-ol compound (6) to    prepare the 3,13-octadecadienyl acetate compound (7).

According to another aspect of the present invention, there is provideda 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the followinggeneral formula (1):

wherein R¹ represents a hydrogen atom, an n-alkyl group having 1 to 9carbon atoms, or a phenyl group.

According to the present invention, it is possible to prepare the3,13-octadecadien-1-ol compound (6) in shorter steps, in a high yield,and in a high purity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 6-Hydroxy-3-hexenylAlkoxymethyl Ether Compound (1)

First, the 6-hydroxy-3-hexenyl alkoxymethyl ether compound of thefollowing general formula (1) will be explained.

R¹ in the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) representsa hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, preferably1 to 5 carbon atoms, more preferably 1 to 2 carbon atoms, or a phenylgroup.

Examples of the n-alkyl group, R¹, include linear saturated hydrocarbongroups such as a methyl group, an ethyl group, an n-propyl group, ann-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group,an n-octyl group, and an n-nonyl group.

Specific examples of the 6-hydroxy-3-hexenyl alkoxymethyl ether compound(1) include the following compounds:

-   (3E)-6-hydroxy-3-hexenyl alkoxymethyl ether compounds such as    (3E)-6-hydroxy-3-hexenyl methoxymethyl ether,    (3E)-6-hydroxy-3-hexenyl ethoxymethyl ether,    (3E)-6-hydroxy-3-hexenyl propoxymethyl ether,    (3E)-6-hydroxy-3-hexenyl butoxymethyl ether,    (3E)-6-hydroxy-3-hexenyl pentyloxymethyl ether,    (3E)-6-hydroxy-3-hexenyl hexyloxymethyl ether,    (3E)-6-hydroxy-3-hexenyl heptyloxymethyl ether,    (3E)-6-hydroxy-3-hexenyl octyloxymethyl ether,    (3E)-6-hydroxy-3-hexenyl nonyloxymethyl ether,    (3E)-6-hydroxy-3-hexenyl decyloxymethyl ether, and    (3E)-6-hydroxy-3-hexenyl benzyloxymethyl ether; and-   (3Z)-6-hydroxy-3-hexenyl alkoxymethyl ether compounds such as    (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl ethoxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl propoxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl butoxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl pentyloxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl hexyloxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl heptyloxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl octyloxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl nonyloxymethyl ether,    (3Z)-6-hydroxy-3-hexenyl decyloxymethyl ether, and    (3Z)-6-hydroxy-3-hexenyl benzyloxymethyl ether.

The 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) may besynthesized, for example, according to a chemical reaction formulacomprising the following two steps.

First, an alkoxymethyl 3-butynyl ether compound of the general formula(9) is reacted with a base and then with ethylene oxide to increase thenumber of carbon atoms to obtain a 6-hydroxy-3-hexynyl alkoxymethylether compound of the general formula (10) (first step). Thecarbon-carbon triple bond of the 6-hydroxy-3-hexynyl alkoxymethyl ethercompound (10) thus obtained is reduced to obtain a 6-hydroxy-3-hexenylalkoxymethyl ether compound (1) (second step).

The aforesaid process for preparing the 6-hydroxy-3-hexenyl alkoxymethylether compound (1) will be explained in more detail below.

The alkoxymethyl 3-butynyl ether compound (9) will be first explainedbelow. R¹ in the general formula (9) is as defined for the generalformula (1).

Specific examples of the alkoxymethyl 3-butynyl ether compound (9)include methoxymethyl 3-butynyl ether, ethoxymethyl 3-butynyl ether,propoxymethyl 3-butynyl ether, butoxymethyl 3-butynyl ether,pentyloxymethyl 3-butynyl ether, hexyloxymethyl 3-butynyl ether,heptyloxymethyl 3-butynyl ether, octyloxymethyl 3-butynyl ether,nonyloxymethyl 3-butynyl ether, decyloxymethyl 3-butynyl ether, andbenzyloxymethyl 3-butynyl ether.

Examples of the base used in the homologation reaction in which thealkoxymethyl 3-butynyl ether compound (9) is reacted with a base andthen with ethylene oxide to increase the number of carbon atoms includeorganometallic reagents such as n-butyllithium, tert-butyllithium,methylmagnesium chloride, methylmagnesium bromide, sodium acetylide, andpotassium acetylide; and metal hydride reagents, such as sodium hydrideand potassium hydride. The organometallic reagents are preferred in viewof the reactivity.

An amount of the base used is preferably 1.0 to 5.0 mol, more preferably1.0 to 2.0 mol, per mol of the alkoxymethyl 3-butynyl ether compound (9)in view of the reactivity.

An amount of the ethylene oxide is preferably 1.0 to 10.0 mol, morepreferably 1.0 to 3.0 mol, per mol of the alkoxymethyl 3-butynyl ethercompound (9) in view of the reactivity.

A solvent may be used in the aforesaid homologation reaction, ifnecessary. Examples of the solvent include usual solvents, for example,ethers such as diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane;hydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; chlorinated solvents such as trichloroethylene, dichloromethane,and chloroform; aprotic polar solvents such as dimethyl sulfoxide,γ-butyrolactone (GBL), N-methylpyrrolidone, N,N-dimethylformamide,N,N-dimethylacetamide, and hexamethylphosphoric triamide; and nitrilessuch as acetonitrile and propionitrile. Ethers such as diethyl ether,tetrahydrofuran, and 4-methyltetrahydropyran are preferred in view ofthe reactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent is preferably 50 to 3,000 g, more preferably100 to 1,200 g, per mol of the alkoxymethyl 3-butynyl ether compound (9)in view of the reactivity.

The 6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) will beexplained below.

R¹ in the general formula (10) is as defined for the general formula(1).

Specific examples of the 6-hydroxy-3-hexynyl alkoxymethyl ether compound(10) include 6-hydroxy-3-hexynyl methoxymethyl ether,6-hydroxy-3-hexynyl ethoxymethyl ether, 6-hydroxy-3-hexynylpropoxymethyl ether, 6-hydroxy-3-hexynyl butoxymethyl ether,6-hydroxy-3-hexynyl pentyloxymethyl ether, 6-hydroxy-3-hexynylhexyloxymethyl ether, 6-hydroxy-3-hexynyl heptyloxymethyl ether,6-hydroxy-3-hexynyl octyloxymethyl ether, 6-hydroxy-3-hexynylnonyloxymethyl ether, 6-hydroxy-3-hexynyl decyloxymethyl ether, and6-hydroxy-3-hexynyl benzyloxymethyl ether.

Examples of the reduction to synthesize the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1) include (i) a catalytic hydrogenation,(ii) a reduction using a zinc compound in an alcohol solvent, (iii) ahydroboration with a dialkylborane, followed by protonation, (iv) areduction using potassium hydroxide and N,N-dimethylformamide (DMF) inthe presence of a palladium catalyst such as palladium acetate, (v) ahydrosilylation to form vinylsilane, followed by desilylation, (vi)hydroalumination, and (vii) a Birch reduction. Preferred are thecatalytic hydrogenation (i), the reduction using a zinc compound (ii),the hydroboration, followed by protonation (iii), and thehydroalumination (vi) in view of the selectivity and productivity. Thecatalytic hydrogenation (i) is preferred, if it is desired to form acarbon-carbon double bond in the 6-hydroxy-3-hexenyl alkoxymethyl ethercompound (1) in a Z-selective manner. The hydroalumination (vi) ispreferred, if it is desired to form a carbon-carbon double bond in the6-hydroxy-3-hexenyl alkoxymethyl ether compound (1) in an E-selectivemanner.

(i) Catalytic Hydrogenation

The catalytic hydrogenation is carried out by supplying hydrogen gas inthe presence of a metal catalyst.

Examples of the metal catalyst used in the catalytic hydrogenationinclude Lindlar catalyst; nickel catalysts such as P-2 nickel boridecatalyst (Thomas J. Caggiano et al. Encyclopedia of Reagents for OrganicSynthesis: 3694-3699) (hereinafter also referred to as “P-2 Nicatalyst”); and palladium catalysts such as palladium carbon and Pd-PEIthat is palladium carbon poisoned by polyethylenimine polymer (PEI). TheLindlar catalyst and nickel catalysts are preferred, in view of theeconomy.

An amount of the metal catalyst varies, depending on a catalyst to beused, and is preferably 0.01 to 50 g per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10), in view of the reactivity, when thecatalyst is solid like Lindlar catalyst. The P-2 Ni catalyst ispreferably used in an amount of 0.001 to 0.50 mol as reduced to a nickelcompound per mol of the 6-hydroxy-3-hexynyl alkoxymethyl ether compound(10).

The solid catalyst may be dispersed in a solvent.

When the metal catalyst is highly active, a catalyst poison may beincorporated, if necessary.

Examples of the catalyst poison include amine compounds such aspyridine, quinoline, and ethylenediamine; phosphorus compounds such astriphenylphosphine, tritolylphosphine, and triethylphosphite; and sulfurcompounds such as benzenethiol, diphenyl sulfide, dimethyl sulfide, anddimethyl sulfoxide.

An amount of the catalyst poison varies greatly, depending on a catalystpoison to be used, and is preferably 0.0001 to 10.0 g per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereaction rate and geometrical selectivity.

Examples of the solvent used in the catalytic hydrogenation includehydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; nitriles such as acetonitrile and propionitrile; esters such asmethyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate;and alcohols such as methanol, ethanol, propanol, butanol, pentanol,hexanol, 2-propanol, 2-butanol, and cyclohexanol.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

When Lindlar catalyst is used, the solvent is preferably a hydrocarbonsuch as hexane, heptane, toluene, or xylene in view of the reactivity.When a nickel catalyst is used, the solvent is preferably an alcoholsuch as methanol, ethanol, propanol, butanol, or 2-propanol in view ofthe reactivity. When a palladium catalyst such as palladium carbon isused, the solvent is preferably an ester such as methyl acetate or ethylacetate in view of the reactivity.

An amount of the solvent used varies, depending on a catalyst and/or asolvent to be used, and is preferably 0 to 1,000 g per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

A reaction temperature of the catalytic hydrogenation varies, dependingon a catalyst and/or a solvent used, and is preferably 0 to 160° C.,more preferably 20 to 100° C., in view of the geometrical selectivity.

A reaction time of the catalytic hydrogenation is preferably 1 to 100hours in view of the yield.

(ii) Reduction Using a Zinc Compound in an Alcohol Solvent

The reduction is carried out using a zinc compound in an alcoholsolvent.

An alcohol used as the solvent has preferably 1 to 10, more preferably 1to 5, carbon atoms. Examples of the alcohol used as the solvent includelinear alcohol compounds such as methanol, ethanol, propanol, butanol,pentanol, hexanol, heptanol, octanol, nonanol, and decanol; branchedalcohol compounds such as 2-propanol and 2-butanol; and cyclic alcoholcompounds such as cyclohexanol. Alcohol compounds having 1 to 5 carbonatoms, such as methanol, ethanol, propanol, butanol, pentanol, and2-propanol, are preferred in view of the reactivity.

An amount of the alcohol is preferably 46 to 1,000 g per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

The zinc compound refers to metallic zinc or activated zinc as explainedbelow.

An amount of the zinc compound is preferably 1.0 to 1,000 mol, morepreferably 1.0 to 200 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of the reactivity.

The reduction may take a longer time due to the low reactivity of zinc.Then, an activator which activates zinc may be added or a zinc compoundwhich has been activated in advance may be used.

Examples of the activator include 1,2-dibromoethane, cuprous chloride,cuprous bromide, cuprous iodide, lithium bromide, iodine, andchlorotrimethylsilane.

The activator may be used alone or in combination thereof, if necessary.

An amount of the activator is preferably 0.01 to 10.0 mol per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

The activated zinc may be prepared, for example, by treating metalliczinc with an acid such as hydrochloric acid; reducing zinc chloride withmetallic lithium in tetrahydrofuran; or reacting metallic zinc with1,2-dibromoethane and lithium dibromocuprate in tetrahydrofuran.

A reaction temperature of the reduction varies, depending on a solventto be used, and is preferably 20 to 120° C. in view of the reactivity.

A reaction time of the reduction is preferably 1 to 150 hours in view ofthe completion of the reaction.

(iii) Hydroboration With a Dialkylborane, Followed by Protonation

For the reduction, hydroboration is first carried out with adialkylborane in a solvent.

The dialkylborane used in the hydroboration has preferably 4 to 18, morepreferably 6 to 12, carbon atoms.

Examples of the dialkylborane include dicyclohexylborane,diisoamylborane, disiamylborane, 9-borabicyclo[3.3.1]nonane (9-BBN),diisopinocampheylborane, catecholborane, and pinacolborane.Dicyclohexylborane and diisoamylborane are preferred in view of thereactivity.

An amount of the dialkylborane is preferably 1.0 to 4.0 mol per mol ofthe 6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

Examples of the solvent used in the hydroboration include ethers such astetrahydrofuran, diethyl ether, dibutyl ether, 4-methyltetrahydropyran,cyclopentylmethyl ether, 1,4-dioxane, and diethyleneglycol dimethylether; and hydrocarbons such as hexane, heptane, benzene, toluene,xylene, and cumene. Ethers such as tetrahydrofuran,4-methyltetrahydropyran, and diethyleneglycol dimethyl ether are morepreferred in view of the reactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent is preferably 100 to 3,000 g per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

A reaction temperature of the hydroboration is preferably -20° C. to 50°C. in view of the geometrical selectivity.

A reaction time of the hydroboration varies, depending on a reactiontemperature and/or a reaction scale, and is preferably 1 to 100 hours inview of the reactivity.

For the reduction, protonation is carried out with an acid in a solventafter the hydroboration.

Examples of the acid used in the protonation include carboxylic acidssuch as acetic acid, propionic acid, butyric acid, pentanoic acid,pivalic acid, heptanoic acid, trifluoroacetic acid, chloroacetic acid,formic acid, and oxalic acid; sulfonic acids such as p-toluenesulfonicacid; and mineral acids such as sulfuric acid, hydrochloric acid, nitricacid, and phosphoric acid. Carboxylic acids such as acetic acid andpropionic acid are preferred in view of the reactivity.

An amount of the acid is preferably 2.0 to 20.0 mol per mol of the6-hydroxy-3-hexynyl alkoxymethyl ether compound (10) in view of thereactivity.

The species and an amount of the solvent are the same as those in thehydroboration, because the protonation is carried out subsequently inthe hydroboration reaction system.

A reaction temperature of the protonation varies, depending on a reagentto be used, and is preferably 0° C. to 150° C. in view of the reactionrate.

A reaction time of the protonation varies, depending on a reactiontemperature and/or a reaction scale, and is preferably 1 to 70 hours inview of the reactivity.

(iv) Reduction Using Potassium Hydroxide and N,N-dimethylformamide (DMF)in the Presence of a Palladium Catalyst such as Palladium Acetate

The reduction is carried out using potassium hydroxide andN,N-dimethylformamide (DMF) in the presence of a palladium catalyst suchas palladium acetate, preferably at 100 to 180° C. for 6 to 100 hours.

(v) Hydrosilylation to Form Vinylsilane, Followed by Desilylation

The hydrosilylation is carried out using a metal catalyst, such asWilkinson catalyst or Trost catalyst, and a trialkylsilane.

An amount of the metal catalyst is preferably 0.0001 to 4.0 mol, morepreferably 0.001 to 1.0 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of the reactivity.

The hydrosilylation is preferably carried out at 5 to 100° C. for 1 to100 hours.

The desilylation after the hydrosilylation is preferably carried outusing, for example, at least one out of acid such as sulfuric acid orhydrochloric acid, hydrogen iodide, acetyl chloride, titaniumtetrachloride, and iodine at 5° C. to 80° C. for 1 to 100 hours.

(vi) Hydroalumination

The hydroalumination is carried out using lithium aluminum hydride.

An amount of lithium aluminum hydride is preferably 0.25 to 4.0 mol,more preferably 0.35 to 2.0 mol, per mol of the 6-hydroxy-3-hexynylalkoxymethyl ether compound (10) in view of the reactivity.

Examples of the solvent used in the hydroalumination include ethers suchas diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, 1,4-dioxane, anddiethyleneglycol dimethyl ether; and hydrocarbons such as hexane,heptane, benzene, toluene, xylene, and cumene. Ethers such astetrahydrofuran, 4-methyltetrahydropyran, and diethyleneglycol dimethylether are preferred in view of the reactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

The hydroalumination is preferably carried out at 20 to 180° C. for 1 to100 hours.

(vii) Birch Reduction

The Birch reduction is carried out using a metal in an amine or alcohol.

Examples of the metal include alkaline metals such as potassium, sodium,and lithium; and alkaline earth metals such as calcium and magnesium.

Examples of the amine include lower amines such as ammonia, methylamine,ethylamine, and propylamine.

Example of the alcohol include methanol, ethanol, and 2-methylpropanol.

The Birch reduction is preferably carried out at -78 to 20° C. for 1 to100 hours.

The geometry of the carbon-carbon double bond of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1) may be constructed selectively in an E-or Z-configuration by choosing reduction conditions.

Preparation of 6-halo-3-hexenyl alkoxymethyl ether compound (2) throughhalogenation

The 6-halo-3-hexenyl alkoxymethyl ether compound (2) may be prepared byhalogenating the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1), asshown in the following chemical reaction formula.

In the halogenation, one or plural species of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1) may be used, if necessary.

For example, a mixture of a (3E)-6-hydroxy-3-hexenyl alkoxymethyl ethercompound (1) and a (3Z)-6-hydroxy-3-hexenyl alkoxymethyl ether compound(1) will give a mixture of a (3E)-6-halo-3-hexenyl alkoxymethyl ethercompound (2) and a (3Z)-6-halo-3-hexenyl alkoxymethyl ether compound(2).

The halogenation reaction for synthesizing 6-halo-3-hexenyl alkoxymethylether compound (2) may be carried out, for example, by tosylating thehydroxyl group with a p-toluenesulfonyl halide compound, followed byhalogenation with a lithium halide compound or by directly halogenatingthe hydroxyl group with a halogenating agent.

Examples of the halogenating agent include halogen molecules such aschlorine, bromine, and iodine; hydrogen halide compounds such ashydrogen chloride, hydrogen bromide, and hydrogen iodide;methanesulfonyl halide compounds such as methanesulfonyl chloride,methanesulfonyl bromide, and methanesulfonyl iodide; benzenesulfonylhalide compounds such as benzenesulfonyl chloride, benzenesulfonylbromide, and benzenesulfonyl iodide; p-toluenesulfonyl halide compoundssuch as p-toluenesulfonyl chloride, p-toluenesulfonyl bromide, andp-toluenesulfonyl iodide; phosphorus halide compounds such asphosphorous trichloride, phosphorous pentachloride, and phosphorustribromide; carbon tetrahalide compounds such as carbon tetrachloride,carbon tetrabromide, and carbon tetraiodide; alkylsilyl halide compoundssuch as tetramethylsilyl chloride, tetramethylsilyl bromide,tetramethylsilyl iodide, triethylsilyl chloride, triethylsilyl bromide,triethylsilyl iodide, triisopropylsilyl chloride, triisopropylsilylbromide, triisopropylsilyl iodide, tert-butyldimethylsilyl chloride,tert-butyldimethylsilyl bromide, and tert-butyldimethylsilyl iodide;oxalyl halide compounds such as oxalyl chloride, oxalyl bromide, andoxalyl iodide; and N-halosuccinimide compounds such asN-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. Amethanesulfonyl halide compound, a benzenesulfonyl halide compound, or ap-toluenesulfonyl halide compound, particularly a methanesulfonyl halidecompound, are more preferred in view of the suppression of sidereactions.

The halogenating agent may be used alone or in combination thereof, ifnecessary. The halogenating agent may be commercially available one.

An amount of the halogenating agent used is preferably 0.8 to 5.0 mol,more preferably 1.0 to 2.5 mol, per mol of the 6-hydroxy-3-hexenylalkoxymethyl ether compound (1).

A base may be incorporated in the halogenation reaction, if necessary.

Examples of the base include hydroxides such as sodium hydroxide,potassium hydroxide, calcium hydroxide, and magnesium hydroxide;carbonates such as sodium carbonate, potassium carbonate, calciumcarbonate, and magnesium carbonate; amines such as triethylamine,N,N-diisopropylethylamine, piperidine, pyrrolidine, pyridine, lutidine,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, and1,8-diazabicyclo[5.4.0]-7-undecene (DBU); and phosphines such astributylphosphine, triphenylphosphine, and tritolylphosphine.

When the halogenating agent is a methanesulfonyl halide compound, abenzenesulfonyl halide compound, or a p-toluenesulfonyl halide compound,the base is preferably an amine, more preferably pyridines such aspyridine, lutidine, or 4-dimethylaminopyridine.

The base may be used alone or in combination thereof, if necessary. Thebase may be commercially available one.

An amount of the base is preferably 0 to 8.0 mol, more preferably 0 to3.0 mol, per mol of the 6-hydroxy-3-hexenyl alkoxymethyl ether compound(1) in view of the yield and/or economy.

A metal salt may be incorporated in the halogenation reaction, ifnecessary.

Examples of the metal salt include lithium salts such as lithiumchloride, lithium bromide, and lithium iodide; sodium salts such assodium chloride, sodium bromide, and sodium iodide; potassium salts suchas potassium chloride, potassium bromide, and potassium iodide; calciumsalts such as calcium chloride, calcium bromide, and calcium iodide; andmagnesium salts such as magnesium chloride, magnesium bromide, andmagnesium iodide.

The metal salt may be used alone or in combination thereof, ifnecessary. The metal salt may be commercially available one.

An amount of the metal salt is preferably 0 to 30.0 mol, more preferably0 to 5.0 mol, per mol of the 6-hydroxy-3-hexenyl alkoxymethyl ethercompound (1) in view of the reactivity.

Although the metal salt increases a concentration of halide ions in thereaction system to thereby enhance the reactivity, it is preferred inview of the economy and/or environmental protection not to incorporatethe metal salt.

A solvent may be incorporated in the halogenation reaction, ifnecessary.

Examples of the solvent include usual solvents, for example, ethers suchas diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane;hydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; chlorinated solvents such as trichloroethylene, dichloromethane,and chloroform; aprotic polar solvents such as dimethyl sulfoxide,γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide(DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamide(HMPA); nitriles such as acetonitrile and propionitrile; and esters suchas methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate.4-Methyltetrahydropyran, dichloromethane, chloroform, γ-butyrolactone,N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, andacetonitrile are preferred, in view of the reactivity. γ-Butyrolactoneand acetonitrile are particularly preferred in view of the safety.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent used in the halogenation reaction is preferably0 to 3,000 g, more preferably 0 to 800 g, per mol of the6-hydroxy-3-hexenyl alkoxymethyl ether compound (1).

The solvent may occupy a part of a reactor space to reduce a space forthe starting materials, resulting in a decreased productivity.Therefore, the reaction may be carried out without a solvent or with thebase as the solvent.

A reaction temperature of the halogenation varies, depending on ahalogenating agent to be used, and is preferably 5 to 180° C. in view ofthe reactivity.

A reaction time of the halogenation reaction varies, depending on ahalogenating agent and/or a reaction scale, and is preferably 0.5 to 100hours in view of the reactivity.

The 6-halo-3-hexenyl alkoxymethyl ether compound (2) will be explainedbelow. X¹ in the general formula (2) represents a halogen atom such as afluorine atom, a chlorine atom, a bromine atom, or an iodine atom. Achlorine atom, a bromine atom, and an iodine atom, particularly achlorine atom and a bromine atom, are preferred in view of the storagestability. R¹ is as defined for the general formula (1).

Specific examples of the 6-halo-3-hexenyl alkoxymethyl ether compound(2) include the following compounds:

-   (3E)-6-chloro-3-hexenyl alkoxymethyl ether compounds such as    (3E)-6-chloro-3-hexenyl methoxymethyl ether, (3E)-6-chloro-3-hexenyl    ethoxymethyl ether, (3E)-6-chloro-3-hexenyl propoxymethyl ether,    (3E)-6-chloro-3-hexenyl butoxymethyl ether, (3E)-6-chloro-3-hexenyl    pentyloxymethyl ether, (3E)-6-chloro-3-hexenyl hexyloxymethyl ether,    (3E)-6-chloro-3-hexenyl heptyloxymethyl ether,    (3E)-6-chloro-3-hexenyl octyloxymethyl ether,    (3E)-6-chloro-3-hexenyl nonyloxymethyl ether,    (3E)-6-chloro-3-hexenyl decyloxymethyl ether, and    (3E)-6-chloro-3-hexenyl benzyloxymethyl ether;-   (3E)-6-bromo-3-hexenyl alkoxymethyl ether compounds such as    (3E)-6-bromo-3-hexenyl methoxymethyl ether, (3E)-6-bromo-3-hexenyl    ethoxymethyl ether, (3E)-6-bromo-3-hexenyl propoxymethyl ether,    (3E)-6-bromo-3-hexenyl butoxymethyl ether, (3E)-6-bromo-3-hexenyl    pentyloxymethyl ether, (3E)-6-bromo-3-hexenyl hexyloxymethyl ether,    (3E)-6-bromo-3-hexenyl heptyloxymethyl ether, (3E)-6-bromo-3-hexenyl    octyloxymethyl ether, (3E)-6-bromo-3-hexenyl nonyloxymethyl ether,    (3E)-6-bromo-3-hexenyl decyloxymethyl ether, and    (3E)-6-bromo-3-hexenyl benzyloxymethyl ether;

(3E)iodo-3-hexenyl alkoxymethyl ether compounds such as(3E)iodo-3-hexenyl methoxymethyl ether, (3E)iodo-3-hexenyl ethoxymethylether, (3E)iodo-3-hexenyl propoxymethyl ether, (3E)iodo-3-hexenylbutoxymethyl ether, (3E)iodo-3-hexenyl pentyloxymethyl ether,(3E)iodo-3-hexenyl hexyloxymethyl ether, (3E)iodo-3-hexenylheptyloxymethyl ether, (3E)iodo-3-hexenyl octyloxymethyl ether,(3E)iodo-3-hexenyl nonyloxymethyl ether, (3E)iodo-3-hexenyldecyloxymethyl ether, and (3E)iodo-3-hexenyl benzyloxymethyl ether;

(3Z)chloro-3-hexenyl alkoxymethyl ether compounds such as(3Z)chloro-3-hexenyl methoxymethyl ether, (3Z)chloro-3-hexenylethoxymethyl ether, (3Z)chloro-3-hexenyl propoxymethyl ether,(3Z)chloro-3-hexenyl butoxymethyl ether, (3Z)chloro-3-hexenylpentyloxymethyl ether, (3Z)chloro-3-hexenyl hexyloxymethyl ether,(3Z)chloro-3-hexenyl heptyloxymethyl ether, (3Z)chloro-3-hexenyloctyloxymethyl ether, (3Z)chloro-3-hexenyl nonyloxymethyl ether,(3Z)chloro-3-hexenyl decyloxymethyl ether, and (3Z)chloro-3-hexenylbenzyloxymethyl ether;

(3Z)bromo-3-hexenyl alkoxymethyl ether compounds such as(3Z)bromo-3-hexenyl methoxymethyl ether, (3Z)bromo-3-hexenylethoxymethyl ether, (3Z)bromo-3-hexenyl propoxymethyl ether,(3Z)bromo-3-hexenyl butoxymethyl ether, (3Z)bromo-3-hexenylpentyloxymethyl ether, (3Z)bromo-3-hexenyl hexyloxymethyl ether,(3Z)bromo-3-hexenyl heptyloxymethyl ether, (3Z)bromo-3-hexenyloctyloxymethyl ether, (3Z)-6-bromo-3-hexenyl nonyloxymethyl ether,(3Z)-6-bromo-3-hexenyl decyloxymethyl ether, and (3Z)-6-bromo-3-hexenylbenzyloxymethyl ether; and

(3Z)iodo-3-hexenyl alkoxymethyl ether compounds such as(3Z)iodo-3-hexenyl methoxymethyl ether, (3Z)iodo-3-hexenyl ethoxymethylether, (3Z)iodo-3-hexenyl propoxymethyl ether, (3Z)iodo-3-hexenylbutoxymethyl ether, (3Z)iodo-3-hexenyl pentyloxymethyl ether,(3Z)iodo-3-hexenyl hexyloxymethyl ether, (3Z)iodo-3-hexenylheptyloxymethyl ether, (3Z)iodo-3-hexenyl octyloxymethyl ether,(3Z)iodo-3-hexenyl nonyloxymethyl ether, (3Z)iodo-3-hexenyldecyloxymethyl ether, and (3Z)iodo-3-hexenyl benzyloxymethyl ether.

As shown in the following chemical reaction formula, the6-halo-3-hexenyl alkoxymethyl ether compound (2) is converted into anucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), which isthen subjected to a coupling reaction with a 12-halo-5-dodecene compound(4) to obtain the 3,13-octadecadiene alkoxymethyl ether compound (5).

Preparation of the Nucleophilic Reagent, 6-(alkoxymethoxy)-3-hexenylCompound (3)

One example of the process for synthesizing the nucleophilic reagent,6-(alkoxymethoxy)-3-hexenyl compound (3) comprises reacting the6-halo-3-hexenyl alkoxymethyl ether compound (2) with magnesium in asolvent to obtain a 6-(alkoxymethoxy)-3-hexenylmagnesium halide compound(3: M = MgZ²) which is a Grignard reagent, as shown in the followingchemical reaction formula. This process is hereinafter referred to as“conversion with magnesium”.

An amount of magnesium used in the conversion with magnesium ispreferably 1.0 to 2.0 grams atom per mol of the 6-halo-3-hexenylalkoxymethyl ether compound (2) in view of the completion of thereaction.

Examples of the solvent used in the conversion with magnesium includeethers such as tetrahydrofuran, diethyl ether, and4-methyltetrahydropyran; and hydrocarbons such as toluene, xylene, andhexane. Ethers such as tetrahydrofuran, diethyl ether, and4-methyltetrahydropyran, particularly tetrahydrofuran, is preferred inview of a reaction rate of the Grignard reagent formation.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent used is preferably 50 to 5,000 g, morepreferably 100 g to 3,000 g, per mol of the 6-halo-3-hexenylalkoxymethyl ether compound (2) in view of the reactivity.

A reaction temperature of the conversion with magnesium varies,depending on a solvent to be used, and is preferably 0 to 120° C. inview of the reactivity.

A reaction time of the conversion with magnesium varies, depending on asolvent and/or a reaction scale to be used, and is preferably 0.5 to 100hours in view of the reactivity.

Another example of the process for synthesizing the nucleophilicreagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), comprises reactingthe 6-halo-3-hexenyl alkoxymethyl ether compound (2) with anorganolithium reagent in a solvent to obtain a6-(alkoxymethoxy)-3-hexenyllithium compound (3: M = Li), as shown in thefollowing chemical reaction formula. This process is hereinafterreferred to as “conversion with an organolithium reagent”)

Examples of the organolithium reagent include linear organolithiumreagents such as methyllithium, ethyllithium, n-propyllithium,n-butyllithium, and n-pentyllithium; and branched organolithium reagentssuch as sec-butyllithium and tert-butyllithium. Methyllithium,n-butyllithium, sec-butyllithium, and tert-butyllithium are preferred inview of the availability.

An amount of the organolithium reagent used is preferably 1.0 to 4.0 molper mol of the 6-halo-3-hexenyl alkoxymethyl ether compound (2) in viewof the reactivity.

Examples of the solvent used in the conversion with an organolithiumreagent include ethers such as tetrahydrofuran, diethyl ether, and4-methyltetrahydropyran; and hydrocarbons such as toluene, xylene, andhexane. A preferable solvent varies, depending on an organolithiumreagent to be used. Generally, tetrahydrofuran, diethyl ether, toluene,or hexane is preferred in view of the reactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent used is preferably 50 to 5,000 g, morepreferably 100 to 3,000 g, per mol of the 6-halo-3-hexenyl alkoxymethylether compound (2) in view of the reactivity.

A reaction temperature of the conversion with an organolithium reagentvaries, depending on a solvent to be used, and is preferably -78 to 25°C. in view of the reactivity.

A reaction time of the conversion with an organolithium reagent varies,depending on a solvent and/or a reaction scale to be used, and ispreferably 0.5 to 100 hours in view of the reactivity.

The nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), willbe explained below.

R¹ in the general formula (3) is as defined for the general formula (1).

M represents Li or MgZ², wherein Z² represents a halogen atom or a6-(alkoxymethoxy)-3-hexenyl group. Examples of the halogen atom, Z²,include a chlorine atom, a bromine atom, and an iodine atom.

Examples of the nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenylcompound (3), include a nucleophilic reagent,(3E)-6-(alkoxymethoxy)-3-hexenyl compound of the following generalformula (3-E), a nucleophilic reagent, (3Z)-6-(alkoxymethoxy)-3-hexenylcompound of the following general formula (3-Z), and a mixture thereof.

Specific examples of the nucleophilic reagent,(3E)-6-(alkoxymethoxy)-3-hexenyl compound (3-E), include the followingcompounds:

-   (3E)-6-(alkoxymethoxy)-3-hexenyllithium compounds such as    (3E)-6-(methoxymethoxy)-3-hexenyllithium,    (3E)-6-(ethoxymethoxy)-3-hexenyllithium,    (3E)-6-(propoxymethoxy)-3-hexenyllithium,    (3E)-6-(butoxymethoxy)-3-hexenyllithium,    (3E)-6-(pentyloxymethoxy)-3-hexenyllithium,    (3E)-6-(hexyloxymethoxy)-3-hexenyllithium,    (3E)-6-(heptyloxymethoxy)-3-hexenyllithium,    (3E)-6-(octyloxymethoxy)-3-hexenyllithium,    (3E)-6-(nonyloxymethoxy)-3-hexenyllithium, and    (3E)-6-(decyloxymethoxy)-3-hexenyllithium; and-   (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium halide compounds,    including (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride    compounds such as (3E)-6-(methoxymethoxy)-3-hexenylmagnesium    chloride, (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(propoxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(butoxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(pentyloxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium chloride,    (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium chloride, and    (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium chloride;    (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium bromide compounds such as    (3E)-6-(methoxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(propoxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(butoxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(pentyloxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium bromide,    (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium bromide, and    (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium bromide; and    (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium iodide compounds such as    (3E)-6-(methoxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(ethoxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(propoxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(butoxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(pentyloxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(hexyloxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(heptyloxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(octyloxymethoxy)-3-hexenylmagnesium iodide,    (3E)-6-(nonyloxymethoxy)-3-hexenylmagnesium iodide, and    (3E)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide.

Among these, (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium halide compoundssuch as (3E)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride compounds arepreferred in view of the availability.

Specific examples of the nucleophilic reagent,(3Z)-6-(alkoxymethoxy)-3-hexenyl compound (3-Z), include the followingcompounds:

-   (3Z)-6-(alkoxymethoxy)-3-hexenyllithium compounds such as    (3Z)-6-(methoxymethoxy)-3-hexenyllithium,    (3Z)-6-(ethoxymethoxy)-3-hexenyllithium,    (3Z)-6-(propoxymethoxy)-3-hexenyllithium,    (3Z)-6-(butoxymethoxy)-3-hexenyllithium,    (3Z)-6-(pentyloxymethoxy)-3-hexenyllithium,    (3Z)-6-(hexyloxymethoxy)-3-hexenyllithium,    (3Z)-6-(heptyloxymethoxy)-3-hexenyllithium,    (3Z)-6-(octyloxymethoxy)-3-hexenyllithium,    (3Z)-6-(nonyloxymethoxy)-3-hexenyllithium, and    (3Z)-6-(decyloxymethoxy)-3-hexenyllithium; and-   (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium halide compounds,    including (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride    compounds such as (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium    chloride, (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(pentyloxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium chloride,    (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium chloride, and    (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium chloride;    (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium bromide compounds such as    (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(pentyloxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium bromide,    (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium bromide, and    (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium bromide; and    (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium iodide compounds such as    (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(ethoxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(propoxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(butoxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(pentyloxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(hexyloxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(heptyloxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(octyloxymethoxy)-3-hexenylmagnesium iodide,    (3Z)-6-(nonyloxymethoxy)-3-hexenylmagnesium iodide, and    (3Z)-6-(decyloxymethoxy)-3-hexenylmagnesium iodide.

Among these, (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium halide compoundssuch as (3Z)-6-(alkoxymethoxy)-3-hexenylmagnesium chloride compounds arepreferred in view of the availability.

One or plural species of the nucleophilic reagent,6-(alkoxymethoxy)-3-hexenyl compound (3), may be used, if necessary.

The nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), maybe commercially available one or may be prepared in house.

For example, a mixture of a nucleophilic reagent,(3E)-6-(alkoxymethoxy)-3-hexenyl compound (3-E), and a nucleophilicreagent, (3Z)-6-(alkoxymethoxy)-3-hexenyl compound (3-Z), will give amixture of the (3E)-3,13-octadecadiene alkoxymethyl ether compound andthe (3Z)-3,13-octadecadiene alkoxymethyl ether compound.

Preparation of 3,13-octadecadiene alkoxymethyl ether compound (5)through a coupling reaction

The nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), issubjected to a coupling reaction with a 12-halo-5-dodecene compound (4)to prepare the 3,13-octadecadiene alkoxymethyl ether compound (5).

First, the 12-halo-5-dodecene compound (4) will be explained below.

X² in the general formula (4) represents a halogen atom such as afluorine atom, a chlorine atom, a bromine atom, or iodine atom. X² ispreferably a chlorine atom, a bromine atom, or an iodine atom, morepreferably a bromine atom or an iodine atom, in view of the reactivity.

Specific examples of the 12-halo-5-dodecene compound (4) include12-fluoro-5-dodecene, 12-chloro-5-dodecene, 12-bromo-5-dodecene, and12-iodo-5-dodecene. 12-Bromo-5-dodecene and 12-iodo-5-dodecene arepreferred in view of the reactivity.

One or plural species of the 12-halo-5-dodecene compound (4) may beused, if necessary.

The 12-halo-5-dodecene compound (4) may be prepared in house, forexample, by deprotonating a terminal alkyne of 1-hexyne, subjecting theproduct to a coupling reaction with a 1,6-dihaloalkane to synthesize a12-halo-5-dodecyne compound, and then reducing the carbon-carbon triplebond into a carbon-carbon double bond. Alternatively, a 1-halo-3-octenecompound is converted into an organometallic reagent, that is, a3-dodecenyl nucleophilic reagent, which is then reacted with a1,4-dihaloalkane compound to obtain the 12-halo-5-dodecene compound (4).

An amount of the nucleophilic reagent, 6-(alkoxymethoxy)-3-hexenylcompound (3), used in the coupling reaction is preferably 0.8 to 3.0mol, more preferably 1.0 to 1.8 mol, per mol of the 12-halo-5-dodecene(4) in view of the economy.

A solvent may be incorporated in the coupling reaction, if necessary.Examples of the solvent include usual solvents, for example, ethers suchas diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane;hydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; chlorinated solvents such as trichloroethylene, dichloromethane,and chloroform; aprotic polar solvents such as dimethyl sulfoxide,γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide(DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamide(HMPA); and nitriles such as acetonitrile and propionitrile. Toluene,tetrahydrofuran, 4-methyltetrahydropyran, or acetonitrile, particularlytetrahydrofuran, is preferred in view of the reactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent used is preferably 30 to 5,000 g, morepreferably 50 to 3,000 g, per mol of the 12-halo-5-dodecene compound (4)in view of the reactivity.

A catalyst may be incorporated in the coupling reaction, if necessary.Examples of the catalyst include copper compounds including cuproushalides such as cuprous chloride, cuprous bromide, and cuprous iodide,and cupric halides such as cupric chloride, cupric bromide, and cupriciodide; iron compounds such as iron(II) chloride, iron(III) chloride,iron(II) bromide, iron(III) bromide, iron(II) iodide, iron(III) iodide,and iron(III) acetylacetonate; silver compounds such as silver chloride,silver nitrate, and silver acetate; titanium compounds such as titaniumtetrachloride, titanium tetrabromide, titanium(IV) methoxide,titanium(IV) ethoxide, titanium(IV) isopropoxide, and titanium (IV)oxide; palladium(II) compounds such asdichlorobis(triphenylphosphine)palladium anddichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium; and nickelcompounds such as nickel chloride,dichloro[1,2-bis(diphenylphosphino)ethane]nickel(II), anddichlorobis(triphenylphosphine)nickel(II). When the nucleophilicreagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), is a Grignardreagent, that is, a 6-(alkoxymethoxy)-3-hexenylmagnesium halide compound(3: M = MgZ²), copper compounds, particularly cuprous halides such ascuprous chloride, cuprous bromide, and cuprous iodide, are preferred inview of the reactivity and/or economy.

The catalyst may be used alone or in combination thereof, if necessary.The catalyst may be commercially available one.

An amount of the catalyst used is preferably 0.0003 to 0.300 mol, morepreferably 0.003 to 0.100 mol, per mol of the 12-halo-5-dodecenecompound (4) in view of the reaction rate and easy post-processing.

When an organolithium reagent is used in the coupling reaction,N,N,N′,N′-tetramethylethylenediamine (TMEDA), hexamethylphosphorictriamide (HMPA), or N,N′-dimethylpropylene urea (DMPU) may be used toimprove a reaction rate, if necessary.

When a catalyst is used in the coupling reaction, a co-catalyst may alsobe incorporated, if necessary. Examples of the co-catalyst include atrialkyl phosphite compound having 3 to 9 carbon atoms, such as triethylphosphite; and an arylphosphine compound having 18 to 44 carbon atoms,such as triphenylphosphine, tritolylphosphine, or2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP). A trialkylphosphite, particularly triethyl phosphite, is preferred in view of thereactivity.

The co-catalyst may be used alone or in combination thereof, ifnecessary. The co-catalyst may be commercially available one.

An amount of the co-catalyst used is preferably 0.0001 to 1.00 mol, morepreferably 0.001 to 0.300 mol, per mol of the 12-halo-5-dodecenecompound (4).

When a catalyst is used in the coupling reaction, a lithium halide mayalso be incorporated, if necessary. Examples of the lithium halideinclude lithium chloride, lithium bromide, and lithium iodide. Lithiumchloride is preferred in view of the reactivity.

An amount of the lithium halide used in the coupling reaction ispreferably 0.0001 to 1.00 mol, more preferably 0.001 to 0.300 mol, permol of the 12-halo-5-dodecene compound (4), in view of the reactivity.

A reaction temperature of the coupling reaction varies, depending on thenucleophilic reagent, 6-(alkoxymethoxy)-3-hexenyl compound (3), and ispreferably -78 to 80° C., more preferably -25 to 40° C. in view of thereactivity.

A reaction time of the coupling reaction varies, depending on a solventand/or a reaction scale, and is preferably 0.5 to 100 hours in view ofthe reactivity.

The 3,13-octadecadiene alkoxymethyl ether compound (5) will be explainedbelow.

R¹ in the general formula (5) is as defined for the general formula (1).

Specific examples of the 3,13-octadecadiene alkoxymethyl ether compound(5) include the following compounds:

-   (3Z,13Z)-3,13-octadecadiene alkoxymethyl ether compounds such as    (3Z,13Z)-3,13-octadecadiene methoxymethyl ether,    (3Z,13Z)-3,13-octadecadiene ethoxymethyl ether,    (3Z,13Z)-3,13-octadecadiene propoxymethyl ether,    (3Z,13Z)-3,13-octadecadiene butoxymethyl ether,    (3Z,13Z)-3,13-octadecadiene pentyloxymethyl ether,    (3Z,13Z)-3,13-octadecadiene hexyloxymethyl ether,    (3Z,13Z)-3,13-octadecadiene heptyloxymethyl ether,    (3Z,13Z)-3,13-octadecadiene octyloxymethyl ether,    (3Z,13Z)-3,13-octadecadiene nonyloxymethyl ether,    (3Z,13Z)-3,13-octadecadiene decyloxymethyl ether, and    (3Z,13Z)-3,13-octadecadiene benzyloxymethyl ether;-   (3Z,13E)-3,13-octadecadiene alkoxymethyl ether compounds such as    (3Z,13E)-3,13-octadecadiene methoxymethyl ether,    (3Z,13E)-3,13-octadecadiene ethoxymethyl ether,    (3Z,13E)-3,13-octadecadiene propoxymethyl ether,    (3Z,13E)-3,13-octadecadiene butoxymethyl ether,    (3Z,13E)-3,13-octadecadiene pentyloxymethyl ether,    (3Z,13E)-3,13-octadecadiene hexyloxymethyl ether,    (3Z,13E)-3,13-octadecadiene heptyloxymethyl ether,    (3Z,13E)-3,13-octadecadiene octyloxymethyl ether,    (3Z,13E)-3,13-octadecadiene nonyloxymethyl ether,    (3Z,13E)-3,13-octadecadiene decyloxymethyl ether, and    (3Z,13E)-3,13-octadecadiene benzyloxymethyl ether;-   (3E,13Z)-3,13-octadecadiene alkoxymethyl ether compounds such as    (3E,13Z)-3,13-octadecadiene methoxymethyl ether,    (3E,13Z)-3,13-octadecadiene ethoxymethyl ether,    (3E,13Z)-3,13-octadecadiene propoxymethyl ether,    (3E,13Z)-3,13-octadecadiene butoxymethyl ether,    (3E,13Z)-3,13-octadecadiene pentyloxymethyl ether,    (3E,13Z)-3,13-octadecadiene hexyloxymethyl ether,    (3E,13Z)-3,13-octadecadiene heptyloxymethyl ether,    (3E,13Z)-3,13-octadecadiene octyloxymethyl ether,    (3E,13Z)-3,13-octadecadiene nonyloxymethyl ether,    (3E,13Z)-3,13-octadecadiene decyloxymethyl ether, and    (3E,13Z)-3,13-octadecadiene benzyloxymethyl ether; and-   (3E,13E)-3,13-octadecadiene alkoxymethyl ether compounds such as    (3E,13E)-3,13-octadecadiene methoxymethyl ether,    (3E,13E)-3,13-octadecadiene ethoxymethyl ether,    (3E,13E)-3,13-octadecadiene propoxymethyl ether,    (3E,13E)-3,13-octadecadiene butoxymethyl ether,    (3E,13E)-3,13-octadecadiene pentyloxymethyl ether,    (3E,13E)-3,13-octadecadiene hexyloxymethyl ether,    (3E,13E)-3,13-octadecadiene heptyloxymethyl ether,    (3E,13E)-3,13-octadecadiene octyloxymethyl ether,    (3E,13E)-3,13-octadecadiene nonyloxymethyl ether,    (3E,13E)-3,13-octadecadiene decyloxymethyl ether, and    (3E,13E)-3,13-octadecadiene benzyloxymethyl ether.

Among these, a 3,13-octadecadiene methoxymethyl ether compound, a3,13-octadecadiene ethoxymethyl ether compound, a 3,13-octadecadienebutoxymethyl ether compound, and a 3,13-octadecadiene benzyloxymethylether compound are preferred in view of the economy.

Preparation of 3,13-octadecadien-1-ol compound (6) throughdealkoxymethylation reaction

The 3,13-octadecadien-1-ol compound (6) may be prepared bydealkoxymethylating the 3,13-octadecadiene alkoxymethyl ether compound(5), as shown in the following chemical reaction formula.

One or plural species of the 3,13-octadecadiene alkoxymethyl ethercompound (5) may be used in the dealkoxymethylation reaction, ifnecessary.

For example, a mixture of a (3Z,13Z)-3,13-octadecadiene alkoxymethylether compound (5) and a (3Z,13E)-3,13-octadecadiene alkoxymethyl ethercompound (5) will give a mixture of (3Z,13Z)-3,13-octadecadien-1-ol (6)and (3Z,13E)-3,13-octadecadien-1-ol (6).

Optimal conditions of the dealkoxymethylation reaction varies, dependingon R¹. For example, when R¹ is a phenyl group, the dealkoxymethylationmay be carried out under Birch reduction conditions in which sodium isused in liquid ammonia. When R¹ is a hydrogen atom or an n-alkyl groupsuch as a methyl group, the dealkoxymethylation may be carried out usingan acid or an alcohol compound (8) mentioned below.

Examples of the acid include inorganic acids such as hydrochloric acidand hydrobromic acid; sulfonic acids such as p-toluenesulfonic acid andbenzenesulfonic acid; organic acids such as trifluoroacetic acid, aceticacid, formic acid, and oxalic acid; and Lewis acids such asiodotrimethylsilane and titanium tetrachloride. p-Toluenesulfonic acid,benzenesulfonic acid, hydrochloric acid, and hydrobromic acid,particularly p-toluenesulfonic acid, hydrochloric acid, and hydrobromicacid, are preferred in view of the suppression of side reactions.

The acid may be used alone or in combination thereof, if necessary. Theacid may be commercially available one.

An amount of the acid used is preferably 0.0001 to 10.0 mol, morepreferably 0.001 to 1.0 mol, per mol of the 3,13-octadecadienealkoxymethyl ether compound (5).

The alcohol compound (8) is represented by the following general formula(8):

R² represents a monovalent hydrocarbon group having 1 to 15 carbonatoms, preferably 1 to 6 carbon atoms, in view of the price oravailability. Examples of the monovalent hydrocarbon group includelinear saturated hydrocarbon groups such as a methyl group, an ethylgroup, an n-propyl group, an n-butyl group, an n-pentyl group, ann-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, ann-decyl group, an n-undecyl group, and an n-dodecyl group; branchedsaturated hydrocarbon groups such as an isopropyl group, a 2-isobutylgroup, and a 2-methylbutyl group; linear unsaturated hydrocarbon groupssuch as a 2-propenyl group; branched unsaturated hydrocarbon groups suchas a 2-methyl-2-propenyl group; cyclic saturated hydrocarbon groups suchas a cyclopropyl group; and isomers thereof. A part of the hydrogenatoms of the hydrocarbon group may be substituted with a methyl group,an ethyl group, or a hydroxyl group.

The monovalent hydrocarbon group is preferably a methyl group, an ethylgroup, an n-propyl group, or an n-butyl group in view of the handling.

Examples of the alcohol compound (8) include linear alcohols such asmethanol, ethanol, n-propanol, n-butanol, n-pentanol, n-hexanol,n-heptanol, n-octanol, n-nonanol, n-decanol, n-undecanol, n-dodecanol,n-tridecanol, n-tetradecanol, and n-pentadecanol; branched alcohols suchas isopropanol and 2-butanol; and diols such as ethyleneglycol,propyleneglycol, 2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol,1,2-dimethyl-1,3-propanediol, 1,3-dimethyl-1,3-propanediol, and2-methyl-1,4-butanediol. Methanol and ethanol, particularly methanol,are preferred in view of the reactivity.

The alcohol compound (8) may be used alone or in combination thereof, ifnecessary.

The alcohol compound (8) may be commercially available one.

An amount of the alcohol compound (8) used is preferably 1 to 1,000 mol,more preferably 1 to 100 mol, per mol of the 3,13-octadecadienealkoxymethyl ether compound (5) in view of the reactivity.

A solvent other than the alcohol compound (8) may be used in thedealkoxymethylation reaction, if necessary.

Examples of the solvent include usual solvents, for example, ethers suchas diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane;hydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; chlorinated solvents such as trichloroethylene, dichloromethane,and chloroform; aprotic polar solvents such as dimethyl sulfoxide,γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide(DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamide(HMPA); nitriles such as acetonitrile and propionitrile; and esters suchas methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

An amount of the solvent used in the dealkoxymethylation reaction ispreferably 0 to 2,000 g, more preferably 0 to 500 g, per mol of the3,13-octadecadiene alkoxymethyl ether compound (5).

The solvent occupies a space of a reactor to reduce a space for startingmaterial, resulting in a decreased productivity. Therefore, thedealkoxymethylation may be carried out without a solvent.

A reaction temperature of the dealkoxymethylation varies, depending on a3,13-octadecadiene alkoxymethyl ether compound (5) to be used, and ispreferably -5 to 180° C. in view of the reactivity.

A reaction time of the dealkoxymethylation varies, depending on a3,13-octadecadiene alkoxymethyl ether compound (5) and/or a reactionscale, and is preferably 0.5 to 100 hours in view of the reactivity.

In the dealkoxymethylation a by-produced alkoxymethoxymethane may bedistilled off from the reaction system, if necessary, whereby theequilibrium is shifted to the product side to reduce the reaction time.

Specific examples of the 3,13-octadecadien-1-ol compound (6) include(3Z,13Z)-3,13-octadecadien-1-ol, (3Z,13E)-3,13-octadecadien-1-ol,(3E,13Z)-3,13-octadecadien-1-ol, and (3E,13E)-3,13-octadecadien-1-ol.

Preparation of 3,13-octadecadienyl Acetate Compound (7) ThroughAcetylation

The 3,13-octadecadienyl acetate compound (7) may be prepared byacetylating the 3,13-octadecadien-1-ol compound (6), as shown in thefollowing chemical reaction formula.

One or plural species of the 3,13-octadecadien-1-ol compound (6) may beused in the acetylation, if necessary.

For example, a mixture of (3Z,13Z)-3,13-octadecadien-1-ol (6) and(3Z,13E)-3,13-octadecadien-1-ol (6) will give a mixture of(3Z,13Z)-3,13-octadecadienyl acetate (7) and(3Z,13E)-3,13-octadecadienyl acetate (7).

The acetylation may be carried out using an acetylating agent.

Examples of the acetylating agent include acid anhydrides such as aceticanhydride; acetyl halide compounds such as acetyl chloride, acetylbromide, and acetyl iodide; and acetic ester compounds such as methylacetate and ethyl acetate. Acetic anhydride and acetyl halide compoundsare preferred in view of the availability.

An amount of the acetylating agent used is preferably 1.0 to 10.0 mol,more preferably 1.0 to 5.0 mol, per mol of the 3,13-octadecadien-1-olcompound (6) in view of the reactivity and economy.

An acid or base may be incorporated in the acetylation, if necessary.

Examples of the acid include mineral acids such as hydrochloric acid,sulfuric acid, and nitric acid; aromatic sulfonic acids such asbenzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such asaluminum trichloride, aluminum ethoxide, aluminum isopropoxide, aluminumoxide, boron trifluoride, boron trichloride, boron tribromide, magnesiumchloride, magnesium bromide, magnesium iodide, zinc chloride, zincbromide, zinc iodide, tin tetrachloride, tin tetrabromide, dibutyltindichloride, dibutyltin dimethoxide, dibutyltin oxide, magnesiumchloride, magnesium bromide, titanium tetrachloride, titaniumtetrabromide, titanium(IV) methoxide, titanium(IV) ethoxide,titanium(IV) isopropoxide, and titanium (IV) oxide.

The acid may be used alone or in combination thereof, if necessary.

An amount of the acid used is preferably 0.001 to 3.00 mol, morepreferably 0.01 to 1.50 mol, per mol of the 3,13-octadecadien-1-olcompound (6) in view of the reactivity and economy.

Examples of the base include trialkylamine compounds such astrimethylamine, triethylamine, and N,N-diisopropylethylamine; cyclicamine compounds such as piperidine, pyrrolidine, and1,8-diazabicyclo[5.4.0]-7-undecene (DBU); aromatic amine compounds suchas pyridine, lutidine, N,N-dimethylaniline, N,N-diethylaniline,N,N-dibutylaniline, and 4-dimethylaminopyridine; and metal alkoxidessuch as sodium methoxide, sodium ethoxide, sodium t-butoxide, sodiumt-amiloxide, lithium methoxide, lithium ethoxide, lithium t-butoxide,lithium t-amiloxide, potassium methoxide, potassium ethoxide, potassiumt-butoxide, and potassium t-amiloxide.

The base may be used alone or in combination thereof, if necessary.

An amount of the base used is preferably 0.010 to 10.0 mol, morepreferably 1.0 to 5.0 mol, per mol of the 3,13-octadecadien-1-olcompound (6), in view of the reactivity and economy.

A solvent may be incorporated in the acetylation, if necessary.

Examples of the solvent include usual solvents, for example, ethers suchas diethyl ether, dibutyl ether, 4-methyltetrahydropyran,tetrahydrofuran (THF), cyclopentylmethyl ether, and 1,4-dioxane;hydrocarbons such as hexane, heptane, benzene, toluene, xylene, andcumene; chlorinated solvents such as trichloroethylene, dichloromethane,and chloroform; aprotic polar solvents such as dimethyl sulfoxide,γ-butyrolactone (GBL), N-methylpyrrolidone (NMP), N,N-dimethylformamide(DMF), N,N-dimethylacetamide (DMAC), and hexamethylphosphoric triamide(HMPA); nitriles such as acetonitrile and propionitrile; and esters suchas methyl acetate, ethyl acetate, n-propyl acetate, and n-butyl acetate.Hydrocarbons such as toluene and xylene are preferred in view of thereactivity.

The solvent may be used alone or in combination thereof, if necessary.The solvent may be commercially available one.

The acetylation may be carried out with or without a solvent, s needed.

An amount of the solvent used in the acetylation is preferably 0 to2,000 g, more preferably 0 to 500 g, per mol of the3,13-octadecadien-1-ol compound (6).

The 3,13-octadecadienyl acetate compound (7) will be explained below.

In the formula (7), Ac represents an acetyl group.

EXAMPLES

The present invention will be described with reference to the followingExamples. It should be noted that the present invention is not limitedto or by the Examples.

The term “purity” as used herein means an area percentage in gaschromatography (GC), unless otherwise specified. The term “productionratio” means a ratio of area percentages in GC. The term “yield” iscalculated from the area percentages determined by GC.

In the Examples, monitoring of the reactions and calculation of theyields were carried out in the following GC conditions.

GC conditions: GC: Capillary gas chromatograph GC-2014 (ShimadzuCorporation); column: DB-WAX (sp-2331), 0.25 µm x 0.25 mmϕ x 30 m;carrier gas: He (1.55 mL/min), detector: FID; column temperature: 150°C., elevated in a rate of 5° C./min, and up to 230° C.

The yield was calculated according to the following equation inconsideration of purities (% GC) of a starting material and a product.

$\begin{array}{l}{\text{Yield}(\%) = \left\{ \left\lbrack \left( {\text{weight of a product obtained by a reation} \times \text{\%GC}} \right) \right) \right)/\text{molecular}} \\{\left( \text{weight of a product} \right\rbrack \div \left\lbrack \left( {\text{weight of a starting material in a reaction} \times \text{\% GC}} \right) \right)/\text{molecular}} \\{\left( \left( \text{weight of a starting material} \right\rbrack \right\} \times \text{100}}\end{array}$

THF represents tetrahydrofuran, GBL represents γ-butyrolactone, P-2Nirepresents P-2 nickel boride, Ms represents a methanesulfonyl group, Merepresents a methyl group, Et represents an ethyl group, Ac representsan acetyl group, and Ph represents a phenyl group.

Example 1: Preparation of 6-hydroxy-3-hexynyl Methoxymethyl Ether (10:R¹ = H)

Methylmagnesium chloride (366.84 g, 4.91 mol) and tetrahydrofuran(1530.16 g) were placed in a reactor at room temperature and stirred at20 to 25° C. for 4 minutes. After the completion of the stirring,3-butynyl methoxymethyl ether (9: R¹ = H) (517.25 g, 4.50 mol, purity99.30 %) was added dropwise to the reactor at 25 to 60° C. After thecompletion of the dropwise addition, the reaction mixture was stirred at60 to 70° C. for 5 hours. Subsequently, ethylene oxide (257.69 g, 5.85mol) was added dropwise at 40 to 60° C. After the completion of thedropwise addition, the reaction mixture was stirred at 60 to 65° C. for3.5 hours. Next, a solution of acetic acid (800.00 g) in water (1600.00g) was added to the reaction mixture, followed by phase separation. Theaqueous phase was removed to obtain the organic phase. The organic phasethus obtained was concentrated at a reduced pressure, and theconcentrate was subjected to distillation at a reduced pressure toobtain 6-hydroxy-3-hexynyl methoxymethyl ether (10: R¹ = H) (635.95 g,3.91 mol, purity 97.16 %, b.p. = 105.6 to 125.1° C./0.40 kPa (3.0 mmHg))in a yield of 86.80 %.

The following are spectrum data of the 6-hydroxy-3-hexynyl methoxymethylether (10: R¹ = H) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ =2.37-2.42 (2H, m), 2.42-2.47 (2H, m), 3.34 (3H, s), 3.60 (2H, t, J = 6.5Hz), 3.64 (2H, t, J = 6.2 Hz), 4.62 (2H, s); ¹³C-NMR(500 MHz, CDCl₃): δ= 20.16, 23.03, 55.17, 61.10, 66.17, 77.77, 79.03, 96.23.

Mass spectrum: EI-mass spectrum (70 eV): m/z 157 (M⁺-1), 127, 109, 97,75, 45.

Infrared absorption spectrum (D-ATR): vmax = 3427, 2936, 2885, 1383,1208, 1150, 1111, 1072, 1040, 918, 849.

Example 2: Preparation of (3Z)-6-hydroxy-3-hexenyl Methoxymethyl Ether(1: R¹ = H)

The 6-hydroxy-3-hexynyl methoxymethyl ether (10: R¹ = H) (635.95 g, 3.91mol, purity 97.16 %) obtained in Example 1 and P-2 Ni catalyst (108.60g) were placed in a reactor at room temperature. The reactor was purgedwith a hydrogen gas at 45 to 55° C. for 7.5 hours with stirring. Theconversion was confirmed to be 100 %, and then water (170.94 g) wasadded to the reaction mixture, followed by phase separation. The aqueousphase was removed to obtain the organic phase. The organic phase thusobtained was concentrated at a reduced pressure, and the concentrate wassubjected to distillation at a reduced pressure to obtain(3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1: R¹ = H) (612.16 g, 3.62mol, purity 94.74 %, b.p. = 107.2 to 111.0° C./0.40 kPa (3.0 mmHg)) in ayield of 92.58 %.

The following are spectrum data of the (3Z)-6-hydroxy-3-hexenylmethoxymethyl ether (1: R¹ = H) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 2.32(2H, dt, J = 6.9 Hz, 6.9 Hz), 2.37 (2H, dt, J = 7.3 Hz, 7.3 Hz), 3.33(3H, s), 3.54 (2H, t, J = 6.5 Hz), 3.61 (2H, t, J = 6.5 Hz), 4.59 (2H,s), 5.46-5.59 (2H, m); ¹³C-NMR (500 MHz, CDCl₃): δ = 27.82, 30.69,55.13, 61.84, 66.87, 96.19, 127.83, 129.16.

Mass spectrum: EI-mass spectrum (70 eV): m/z 159 (M⁺-1), 130, 111, 100,81, 68, 55, 45.

Infrared absorption spectrum (D-ATR): vmax = 3423, 2932, 2883, 1442,1404, 1150, 1109, 1035, 919, 725.

Example 3: Preparation of (3E)-6-hydroxy-3-hexenyl Methoxymethyl Ether(1: R¹ = H)

Lithium aluminum hydride (42.50 g, 1.12 mol) and diethyleneglycoldimethyl ether (666.24 g) were placed in a reactor at room temperatureand stirred at 50 to 55° C. for 15 minutes. After the completion of thestirring, the 6-hydroxy-3-hexynyl methoxymethyl ether (260.85 g, 1.60mol, purity 97.03 %) obtained according to Example 1 was added dropwiseat 50 to 60° C. and stirred at 130 to 135° C. for 20 hours. Aftercooling to 20 to 25° C., tetrahydrofuran (2508.78 g), water (42.50 g),an aqueous solution (170.03 g) of sodium hydroxide (0.16 mol), andCelite (529.51 g) were sequentially added, and stirred for 12 hours.After the completion of the stirring, the reaction mixture was filteredto obtain the organic phase. The organic phase thus obtained wasconcentrated at a reduced pressure, and the concentrate was subjected todistillation at a reduced pressure to obtain (3E)-6-hydroxy-3-hexenylmethoxymethyl ether (1: R¹ = H) (235.15 g, 1.44 mol, purity 98.13 %,b.p. = 104.3 to 105.6° C./0.40 kPa (3.0 mmHg)) in a yield of 90.02 %.

The following are spectrum data of the (3E)-6-hydroxy-3-hexenylmethoxymethyl ether (1: R¹ = H) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 1.89(1H, br. s), 2.25 (2H, ddt, J = 0.8 Hz, 6.5 Hz, 6.5 Hz), 2.30 (2H, ddt,J = 0.8 Hz, 6.9 Hz, 6.9 Hz), 3.33 (3H, s), 3.54 (2H, t, J = 6.9 Hz),3.60 (2H, t, J = 6.5 Hz), 4.59 (2H, s), 5.43-5.58 (2H, m); ¹³C-NMR (500MHz, CDCl₃): δ = 33.02, 35.96, 55.09, 61.77, 67.24, 96.29, 128.27,129.91.

Mass spectrum: EI-mass spectrum (70 eV)— m/z 159 (M⁺-1), 130, 100, 81,68, 55, 45.

Infrared absorption spectrum (D-ATR): vmax = 3410, 2931, 2885, 1442,1383, 1211, 1150, 1110, 1043, 970, 919.

Example 4: Preparation of (3Z)-6-hydroxy-3-hexenyl Butoxymethyl Ether(1: R¹ = CH₂CH₂CH₃)

The procedures of Examples 1 and 2 were repeated with the exception that3-butynyl butoxymethyl ether (9: R¹ = CH₂CH₂CH₃) (276.94 g, 1.52 mol,purity 85.75 %) was used instead of 3-butynyl methoxymethyl ether as astarting material, so that (3Z)-6-hydroxy-3-hexenyl butoxymethyl ether(1: R¹ = CH₃CH₂CH₂) (251.00 g, 1.20 mol, purity 96.42 %, b.p. = 122.0 to126.9° C./0.40 kPa (3.0 mmHg)) was obtained in a yield of 78.71 % afterthe two steps.

The following are spectrum data of the (3Z)-6-hydroxy-3-hexenylbutoxymethyl ether (1: R¹ = CH₃CH₂CH₂) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.91(3H, t, J = 7.3 Hz), 1.31-1.41 (2H, m), 1.51-1.59 (2H, m), 2.17 (1H, br.s), 2.33 (2H, dt, J = 6.7 Hz, 6.7 Hz), 2.37 (2H, dt, J = 6.7 Hz, 6.7Hz), 3.50 (2H, t, J = 6.5 Hz), 3.56 (2H, t, J = 6.5 Hz), 3.62 (2H, t, J= 6.1 Hz), 4.64 (2H, s), 5.50 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz),5.56 (1H, dtt, J = 11.1 Hz, 7.3 Hz, 1.2 Hz); ¹³C-NMR (500 MHz, CDCl₃): δ= 13.81, 19.31, 27.85, 30.70, 31.70, 61.87, 66.83, 67.61, 95.08, 127.80,129.32.

Mass spectrum: EI-mass spectrum (70 eV): m/z 201 (M⁺-1), 185, 129, 111,99, 87, 69, 57, 41, 29.

Infrared absorption spectrum (D-ATR): vmax = 3431, 2957, 2933, 2873,1465, 1380, 1146, 1115, 1045, 828, 725.

Example 5: Preparation of (3Z)-6-hydroxy-3-hexenyl Benzyloxymethyl Ether(1: R¹= Ph)

The procedures of Examples 1 and 2 were repeated with the exception that3-butynyl benzyloxymethyl ether (9: R¹ = Ph) (190.79 g, 0.95 mol, purity95.21 %) was used instead of 3-butynyl methoxymethyl ether as a startingmaterial, so that (3Z)-6-hydroxy-3-hexenyl benzyloxymethyl ether (1: R¹= Ph) (163.56 g, 0.65 mol, purity 94.20 %, b.p. = 160.0 to 163.7°C./0.40 kPa (3.0 mmHg)) was obtained in a yield of 68.28 %.

The following are spectrum data of the (3Z)-6-hydroxy-3-hexenylbenzyloxymethyl ether (1: R¹ = Ph) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 2.06(1H, br. s), 2.35 (2H, dt, J = 6.6 Hz, 6.6 Hz), 2.40 (2H, dt, J = 6.6Hz, 6.6 Hz), 3.64 (2H, t, J = 6.5 Hz), 3.64 (2H, t, J = 6.2 Hz), 4.60(2H, s), 4.76 (2H, s), 5.52 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.6 Hz), 5.59(1H, J = 11.1 Hz, 7.3 Hz, 1.1 Hz), 7.27-7.37 (5H, m); ¹³C-NMR (500 MHz,CDCl₃): δ = 27.85, 30.73, 61.90, 67.13, 69.39, 94.49, 127.65, 127.85,127.87, 128.36, 129.28, 137.81.

Mass spectrum: EI-mass spectrum (70 eV): m/z 235 (M⁺-1), 218, 206, 160,129, 108, 91, 77, 65, 53, 41, 29.

Infrared absorption spectrum (D-ATR): vmax = 3420, 2939, 2877, 1454,1379, 1164, 1110, 1046, 1027, 737, 698.

Example 6: Preparation of (3Z)-6-chloro-3-hexenyl Methoxymethyl Ether(2: R¹ = H, X¹ = Cl)

The (3Z)-6-hydroxy-3-hexenyl methoxymethyl ether (1: R¹ = H) (541.14 g,3.20 mol, purity 94.74 %) obtained in Example 2, pyridine (455.62 g,5.76 mol), and GBL (960.00 g) were placed in a reactor and stirred at 0to 10° C. for 26 minutes.

Subsequently, methanesulfonyl chloride (513.18 g, 4.48 mol) was addeddropwise at 0 to 10° C. After the completion of the dropwise addition,the reaction mixture was heated to 60 to 65° C. and stirred for 5 hours.After the completion of the stirring, water (1280.00 g) and hexane(1280.00 g) were sequentially added to the reaction mixture, followed byphase separation. The aqueous phase was removed to obtain the organicphase. The organic phase thus obtained was washed with a solution ofacetic acid (160.00 g) in water (1280.00 g), and then washed with asolution of sodium bicarbonate (80.00 g) in water (1280.00 g). Theorganic phase thus obtained was concentrated at a reduced pressure. Theconcentrate was subjected to distillation at a reduced pressure toobtain (3Z)-6-chloro-3-hexenyl methoxymethyl ether (2: R¹= H, X¹ = Cl)(496.72 g, 2.71 mol, purity 97.33 %, b.p. = 80.0 to 82.9° C./0.40 kPa(3.0 mmHg)) in a yield of 84.57 %.

The following are spectrum data of the (3Z)-6-chloro-3-hexenylmethoxymethyl ether (2: R¹ = H, X¹ = Cl) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 2.36(2H, dt, J = 6.5 Hz, 6.5 Hz), 2.53 (2H, dt, J = 7.1 Hz, 7.1 Hz), 3.35(3H, s), 3.51 (2H, t, J = 6.9 Hz), 3.54 (2H, t, J = 6.9 Hz), 4.61 (2H,s), 5.49 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz), 5.57 (1H, dtt, J = 10.7Hz, 7.3 Hz, 1.6 Hz); ¹³C-NMR (500 MHz, CDCl₃): δ = 28.03, 30.71, 44.01,55.12, 66.98, 96.32, 127.08, 128.98.

Mass spectrum: EI-mass spectrum (70 eV): m/z 177 (M⁺-1), 147, 129, 112,97, 75, 65, 55, 45, 29.

Infrared absorption spectrum (D-ATR): vmax = 2951, 2884, 1444, 1381,1296, 1209, 1148, 1111, 1036, 919, 738, 661.

Example 7: Preparation of (3Z,13Z)-3,13-octadiene Methoxymethyl Ether(5: R¹ = H)

Magnesium (15.24 g, 0.63 grams atom) and tetrahydrofuran (171.00 g) wereplaced in a reactor at room temperature and stirred at 60 to 65° C. for9 minutes. After the completion of the stirring, the(3Z)-6-chloro-3-hexenyl methoxymethyl ether (2: R¹ = H, X¹ = Cl) (109.86g, 0.60 mol, purity 97.33 %) obtained in Example 6 was added dropwise at60 to 75° C. After the completion of the dropwise addition, the reactionmixture was stirred at 75 to 80° C. for 2 hours to prepare(3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3: R¹ = H, M =MgCl).

Subsequently, cuprous chloride (0.64 g, 0.0065 mol), lithium chloride(0.44 g, 0.010 mol), triethyl phosphite (6.39 g, 0.038 mol),tetrahydrofuran (114.00 g), and (5Z)-12-bromo-5-dodecene (4: X² = Br)(140.92 g, 0.57 mol, purity 100 %) were placed in another reactor, andthe (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3: R¹ = H, M =MgCl) prepared above was added dropwise at 15 to 30° C. After thecompletion of the dropwise addition, the reaction mixture was stirred at15 to 25° C. for 2.5 hours. Next, a solution of ammonium chloride (6.28g) in water (163.01 g) and hydrochloric acid (11.98 g, 0.066 mol ofhydrogen chloride) were added sequentially to the reaction mixture,followed by phase separation and removal of the aqueous phase. Theorganic phase thus obtained was concentrated at a reduced pressure, andthe concentrate was subjected to distillation at a reduced pressure toobtain (3Z,13Z)-3,13-octadiene methoxymethyl ether (5: R¹ = H) (163.39g, 0.49 mol, purity 92.36 %, b.p. = 150.5 to 156.1° C./0.40 kPa (3.0mmHg)) in a yield of 85.27 %.

The following are spectrum data of the (3Z,13Z)-3,13-octadienemethoxymethyl ether (5: R¹ = H) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.89(3H, t, J = 7.3 Hz), 1.24-1.38 (16H, m), 1.96-2.07 (6H, m), 2.34 (2H,q-like, J = 6.9 Hz), 3.36 (3H, s), 3.53 (2H, t, J = 7.3 Hz), 4.62 (2H,s), 5.32-5.41 (3H, m), 5.47 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz);¹³C-NMR (500 MHz, CDCl₃): δ = 13.97, 22.33, 26.89, 27.16, 27.33, 27.88,29.27, 29.49, 29.59, 29.74, 31.95, 55.10, 67.40, 96.32, 125.34, 129.82,129.84, 132.19.

Mass spectrum: EI-mass spectrum (70 eV): m/z 310 (M⁺), 278, 248, 219,151, 135, 109, 81, 45, 29.

Infrared absorption spectrum (D-ATR): vmax = 2925, 2854, 1465, 1379,1151, 1111, 1074, 1037, 920, 723.

Example 8: Preparation of (3Z,13Z)-3,13-octadecadien-1-ol (6)

The (3Z,13Z)-3,13-octadiene methoxymethyl ether (5: R¹ = H) (157.99 g,0.47 mol, purity 92.36 %) obtained in Example 7, methanol (234.95 g,7.33 mol), and 20 % hydrochloric acid (23.50 g, 0.13 mol of hydrogenchloride) were placed in a reactor equipped with a distillation tower,and the reaction mixture was heated to 60° C. and stirred for 1 hour.After the completion of the stirring, the internal temperature wasraised to 65 to 70° C. to distill off a mixture of by-produceddimethoxymethane and methanol from the distillation tower. The reactionmixture was sampled during the reaction. After the conversion wasconfirmed to be 100 %, water (140.97 g) was added to the reactionmixture, followed by phase separation. The aqueous phase was removed toobtain the organic phase. The organic phase thus obtained was subjectedto distillation at a reduced pressure to obtain(3Z,13Z)-3,13-octadecadien-1-ol (6) (127.12 g, 0.44 mol, purity 91.56 %,b.p. = 160.0 to 165.8° C./0.40 kPa (3.0 mmHg)) in a yield of 92.96 %.

The following are spectrum data of the (3Z,13Z)-3,13-octadecadien-1-ol(6) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.89(3H, t, J = 7.3 Hz, 1.24-1.38 (16H, m), 1.54 (1H, br. s), 1.98-2.09 (6H,m), 2.32 (2H, q-like, J = 6.7 Hz), 3.63 (2H, t, J = 6.5 Hz), 5.30-5.40(3H, m), 5.55 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz); ¹³C-NMR (500 MHz,CDCl₃): δ = 13.96, 22.32, 26.89, 27.16, 27.34, 29.26, 29.47, 29.68,29.73, 30.77, 31.94, 62.31, 124.91, 129.84, 133.51.

Mass spectrum: EI-mass spectrum (70 eV): m/z 266 (M⁺), 248, 222, 208,194, 177, 163, 149, 135, 121, 109, 95, 81, 55, 41.

Infrared absorption spectrum (D-ATR): vmax = 3333, 2925, 2854, 1465,1049, 722.

Example 9: Preparation of (3Z,13Z)-3,13-octadecadienyl Acetate (7)

The (3Z,13Z)-3,13-octadecadien-1-ol (6) (104.31 g, 0.36 mol, purity91.56 %) obtained in Example 8, toluene (78.56 g), and pyridine (53.86g, 0.68 mol) were placed in a reactor at room temperature and stirred at15 to 25° C. for 2 minutes. After the completion of the stirring, aceticanhydride (153.14 g, 0.54 mol) was added dropwise at 20 to 40° C. andstirred at 30 to 35° C. for 6.5 hours. Next, water (94.14 g) was addedto the reaction mixture, followed by phase separation. The aqueous phasewas removed to obtain the organic phase. The organic phase thus obtainedwas subjected to distillation at a reduced pressure to obtain(3Z,13Z)-3,13-octadecadienyl acetate (7) (116.35 g, 0.36 mol, purity95.03, b.p. = 136.9 to 145.1° C./0.40 kPa (3.0 mmHg)) in a yield of 100%.

The following are spectrum data of the (3Z,13Z)-3,13-octadecadienylacetate (7) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.89(3H, t, J = 7.3 Hz), 1.24-1.38 (16H, m), 1.98-2.06 (6H, m), 2.04 (3H,s), 2.37 (2H, q-like, J = 7.1 Hz), 4.05 (2H, t, J = 6.9 Hz), 5.30-5.38(3H, m), 5.50 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz); ¹³C-NMR (500 MHz,CDCl₃): δ = 13.96, 20.94, 22.32, 26.79, 26.89, 27.16, 27.28, 29.25,29.47, 29.49, 29.57, 29.73, 31.94, 63.96, 124.21, 129.83, 132.97,171.08.

Mass spectrum: EI-mass spectrum (70 eV): m/z 308 (M⁺), 248, 219, 191,163, 135, 109, 81, 65, 43.

Infrared absorption spectrum (D-ATR): vmax = 2926, 2854, 1745, 1465,1383, 1363, 1237, 1036, 723.

Example 10: Preparation of (3Z,13E)-3,13-octadiene Methoxymethyl Ether(5: R¹ = H)

Magnesium (5.07 g, 0.21 grams atom) and tetrahydrofuran (59.78 g) wereplaced in a reactor at room temperature and stirred at 60 to 65° C. for16 minutes. After the completion of the stirring, the(3Z)-6-chloro-3-hexenyl methoxymethyl ether (2: R¹ = H, X¹ = Cl) (36.58g, 0.20 mol, purity 97.33 %) obtained in Example 6 was added dropwise at60 to 75° C. After the completion of the dropwise addition, the reactionmixture was stirred at 75 to 80° C. for 2 hours to prepare(3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3: R¹ = H, M =MgCl).

Subsequently, cuprous chloride (0.21 g, 0.0021 mol), lithium chloride(0.15 g, 0.0035 mol), triethyl phosphite (2.13 g, 0.013 mol),tetrahydrofuran (37.96 g), and (5E)-12-bromo-5-dodecene (4: X² = Br)(47.23 g, 0.19 mol, purity 99.37 %) were placed in another reactor, andthe (3Z)-6-(methoxymethoxy)-3-hexenylmagnesium chloride (3: R¹ = H, M =MgCl) prepared above was added dropwise at 15 to 30° C. After thecompletion of the dropwise addition, the reaction mixture was stirred at15 to 25° C. for 3 hours. After the completion of the stirring, anaqueous solution of ammonium chloride (2.09 g) in water (54.28 g) andhydrochloric acid (3.99 g, 0.022 mol of hydrogen chloride) were addedsequentially to the reaction mixture, followed by phase separation. Theaqueous phase was removed to obtain the organic phase. The organic phasethus obtained was concentrated at a reduced pressure, and theconcentrate was subjected to distillation at a reduced pressure toobtain (3Z,13E)-3,13-octadiene methoxymethyl ether (5: R¹ = H) (59.78 g,0.18 mol, purity 92.42 %, b.p. = 130.0 to 145.9° C./0.40 kPa (3.0 mmHg))in a yield of 93.75 %.

The following are spectrum data of the (3Z,13E)-3,13-octadienemethoxymethyl ether (5: R¹ = H) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.88(3H, t, J = 7.3 Hz), 1.23-1.38 (16H, m), 1.93-2.00 (4H, m), 2.04 (2H,dt, J = 7.3 Hz, 7.3 Hz), 2.34 (2H, q-like, J = 6.9 Hz), 3.36 (3H, s),3.53 (2H, t, J = 6.9 Hz), 4.62 (2H, s), 5.32-5.43 (3H, m), 5.47 (1H,dtt, J = 10.7 Hz, 7.3 Hz, 1.6 Hz); ¹³C-NMR (500 MHz, CDCl₃): δ = 13.94,22.17, 27.33, 27.88, 29.14, 29.27, 29.46, 29.49, 29.59, 29.63, 31.82,32.27, 32.58, 55.10, 67.40, 96.32, 125.33, 130.29, 130.31, 132.20.

Mass spectrum: EI-mass spectrum (70 eV): m/z 310 (M⁺), 278, 248, 221,151, 135, 109, 81, 45, 29.

Infrared absorption spectrum (D-ATR): vmax = 2925, 2854, 1465, 1151,1111, 1037, 967, 920, 724.

Example 11: Preparation of (3Z,13E)-3,13-octadecadien-1-ol (6)

The (3Z,13E)-3,13-octadiene methoxymethyl ether (5: R¹ = H) (59.54 g,0.18 mol, purity 92.42 %) obtained in Example 10, methanol (88.60 g,2.77 mol), and 20 % hydrochloric acid (8.86 g, 0.045 mol of hydrogenchloride) were placed in a reactor equipped with a distillation tower,and the reaction mixture was heated to 60° C. and stirred for 1 hour.After the completion of the stirring, the internal temperature wasraised to 65 to 70° C. to distill off a mixture of by-produceddimethoxymethane and methanol from the distillation tower. The reactionmixture was sampled during the reaction. After the conversion wasconfirmed to be 100 %, water (53.16 g) was added to the reactionmixture, followed by phase separation. The aqueous phase was removed toobtain the organic phase. The organic phase thus obtained was subjectedto distillation at a reduced pressure to obtain(3Z,13E)-3,13-octadecadien-1-ol (6) (47.35 g, 0.16 mol, purity 91.11 %,b.p. = 131.2 to 150.0° C./0.40 kPa (3.0 mmHg)) in a yield of 91.34 %.

The following are spectrum data of the (3Z,13E)-3,13-octadecadien-1-ol(6) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.88(3H, t, J = 7.3 Hz), 1.22-1.38 (16H, m), 1.54 (1H, br. s), 1.93-2.00(4H, m), 2.05 (2H, q-like, J = 6.9 Hz), 2.32 (2H, q-like, J = 6.9 Hz),3.63 (2H, t, J = 6.5 Hz), 5.32-5.42 (3H, m), 5.55 (1H, dtt, J = 11.1 Hz,7.3 Hz, 1.6 Hz); ¹³C-NMR (500 MHz, CDCl₃): δ = 13.93, 22.16, 27.34,29.12, 29.27, 29.44, 29.47, 29.61, 29.67, 30.76, 31.81, 32.26, 32.57,62.30, 124.89, 130.29, 133.52.

Mass spectrum: EI-mass spectrum (70 eV): m/z 266 (M⁺), 248, 222, 208,194, 177, 163, 149, 135, 121, 109, 95, 81, 55, 41.

Infrared absorption spectrum (D-ATR): vmax = 3330, 2924, 2854, 1465,1049, 967, 723.

Example 12: Preparation of (3Z,13E)-3,13-octadecadienyl Acetate (7)

The (3Z,13E)-3,13-octadecadien-1-ol (6) (44.25 g, 0.15 mol, purity 91.11%) obtained in Example 11, toluene (33.16 g), and pyridine (22.74 g,0.29 mol) were placed in a reactor at room temperature and stirred at 15to 25° C. for 2 minutes. After the completion of the stirring, aceticanhydride (23.17 g, 0.23 mol) was added dropwise at 20 to 40° C. andstirred at 30 to 35° C. for 7 hours. Next, water (39.74 g) was added tothe reaction mixture, followed by phase separation. The aqueous phasewas removed to obtain the organic phase. The organic phase thus obtainedwas subjected to distillation at a reduced pressure to obtain(3Z,13E)-3,13-octadecadienyl acetate (7) (46.68 g, 0.15 mol, purity95.68, b.p. = 133.9 to 141.2° C./0.40 kPa (3.0 mmHg)) in a yield of 100%.

The following are spectrum data of the (3Z,13E)-3,13-octadecadienylacetate (7) thus prepared.

Nuclear magnetic resonance spectrum: ¹H-NMR (500 MHz, CDCl₃): δ = 0.88(3H, t, J = 7.3 Hz), 1.22-1.38 (16H, m), 1.93-1.99 (4H, m), 2.03 (2H,q-like, J = 6.9 Hz), 2.04 (3H, s), 2.37 (2H, q-like, J = 7.1 Hz), 4.05(2H, t, J = 6.9 Hz), 5.33 (1H, dtt, J = 11.1 Hz, 7.3 Hz, 1.5 Hz),5.36-5.40 (2H, m), 5.50 (1H, dtt, J = 10.7 Hz, 7.3 Hz, 1.5 Hz); ¹³C-NMR(500 MHz, CDCl₃): δ = 13.93, 20.95, 22.16, 26.78, 27.29, 29.13, 29.25,29.44, 29.49, 29.58, 29.62, 31.81, 32.26, 32.58, 63.96, 124.20, 130.30,132.98, 171.08.

Mass spectrum: EI-mass spectrum (70 eV): m/z 308 (M⁺), 248, 219, 191,163, 135, 109, 81, 65, 43.

Infrared absorption spectrum (D-ATR): vmax = 2925, 2854, 1745, 1465,1363, 1237, 1036, 967, 724.

1. A 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the followinggeneral formula (1):

wherein R¹ represents a hydrogen atom, an n-alkyl group having 1 to 9carbon atoms, or a phenyl group.